Implantable heart stimulators can be used for cardiac rhythm management (CRM) for treating a variety of functional and rhythm disorders of the heart, such as bradycardia, tachycardia or fibrillation, by way of electric stimulation pulses delivered to the myocardium (i.e., the heart tissue). A sufficiently strong stimulation pulse outside a heart chamber's refractory period leads to excitation of the myocardium of that heart chamber, which in turn is followed by a contraction of the respective heart chamber.
Depending on the disorder to be treated, such heart stimulators generate electrical stimulation pulses that are delivered to the heart tissue (myocardium) of a respective heart chamber according to an adequate timing regime. Delivery of stimulation pulses to the myocardium is usually achieved by means of an electrode lead that is electrically connected to a stimulation pulse generator inside a heart stimulator's housing. The electrode lead typically carries a stimulation electrode in the region of its distal end. A stimulation pulse also is called a pace.
Similarly, pacing a heart chamber means stimulating a heart chamber by delivery of a stimulation pulse.
In order to be able to sense the contraction of a heart chamber, which occurs naturally without artificial stimulation and which is called an intrinsic contraction, the heart stimulator usually includes at least one sensing stage that is connected to a sensing electrode placed in or near the heart chamber. An intrinsic excitation of a heart chamber results in characteristic electrical potentials that can be picked up via the sensing electrode and that can be evaluated by the sensing stage in order to determine whether an intrinsic excitation—called an intrinsic event—has occurred.
Usually, a heart stimulator features separate stimulation pulse generators for each heart chamber to be stimulated. Therefore, in a dual chamber pacemaker, usually an atrial and a ventricular stimulation pulse generator for generating atrial and ventricular stimulation pulses is are provided. Delivery of an atrial or a ventricular stimulation pulse causing an artificial excitation of the atrium or the ventricle, respectively, is called an atrial stimulation event AP (atrial paced event) or a ventricular stimulation event VP (ventricular paced event), respectively.
Similarly, common heart stimulators feature separate sensing stages for each heart chamber of interest. In a dual chamber pacemaker usually two separate sensing stages, an atrial sensing stage and a ventricular sensing stage, are provided. The sensing stages are capable of detecting intrinsic atrial events AS (atrial sensed event) or intrinsic ventricular events VS (ventricular sensed event), respectively.
In a heart cycle, an excitation of the myocardium leads to a depolarization of the myocardium that leads to a contraction of the heart chamber. If the myocardium is fully depolarized it is unsusceptible to further excitation and is thus refractory. Thereafter, the myocardium repolarizes and thus relaxes and the heart chamber expands again. In a typical intracardiac electrogram (IEGM), depolarization of the ventricle corresponds to a signal known as the “R-wave”. The repolarization of the ventricular myocardium coincides with a signal known as the “T-wave”. Atrial depolarization is manifested by a signal known as the “P-wave”.
In a healthy heart, initiation of the cardiac cycle normally begins with depolarization of the sinoatrial (SA) node. This specialized structure is located in the upper portion of the right atrium wall and acts as a natural “pacemaker” of the heart. In a normal cardiac cycle and in response to the initiating SA depolarization, the right atrium contracts and forces the blood that has accumulated therein into the ventricle. The natural stimulus causing the right atrium to contract is conducted to the right ventricle via the atrioventricular node (AV node) with a short, natural delay referred to as the atrioventricular delay (AV-delay). Thus, a short time after the right atrial contraction (a time sufficient to allow the bulk of the blood in the right atrium to flow through the one-way valve into the right ventricle), the right ventricle contracts, forcing the blood out of the right ventricle to the pulmonary artery. A typical time interval between contraction of the right atrium and contraction of the right ventricle might is be 200 ms; a typical time interval between contraction of the right ventricle and the next contraction of the right atrium might be 800 ms. Thus, it is a right atrial contraction (A), followed a relatively short time thereafter by a right ventricle contraction (V), followed a relatively long time thereafter by the next right atrial contraction, that produces the desired AV synchrony. Where AV synchrony exists, the heart functions very efficiently as a pump in delivering life-sustaining blood to body tissue; where AV synchrony is absent, the heart functions as an inefficient pump (for example due to the loss of atrial kick when AV-delay is too short or due to diastolic regurgitation when AV-delay is too long).
Similarly, the left ventricle contracts in synchrony with the right atrium and the right ventricle with a positive or negative time delay between a right ventricular contraction and a left ventricular contraction.
A pacemaker generally shall induce a contraction of a heart chamber by delivery of a stimulation pulse (pacing pulse) to the chamber when no natural (intrinsic) contraction of the chamber occurs in due time. A contraction of a heart chamber often is called an “event”.
Since a contraction may be an intrinsic contraction, which can be sensed by a sensing stage of a pacemaker, such an event is called a sensed event. A contraction due to delivery of a stimulation pulse is called a paced event. A sensed event in the atrium is called As, a paced atrial event is called Ap. Similarly, a sensed event in the ventricle is called Vs and a paced ventricular event is called Vp.
To mimic the natural behavior of a heart, a dual-chamber pacemaker provides for an AV-delay timer to provide for an adequate time delay (atrioventricular delay, AV-delay, AVD) between a natural (intrinsic) or a stimulated (paced) right atrial contraction and a right ventricular contraction. In a similar way a biventricular pacemaker provides for an adequate time delay (VV-delay, VVD) between a right ventricular contraction and a left ventricular contraction.
The time delay for a left ventricular (stimulated, paced) contraction may be timed from a scheduled right ventricular contraction which has not yet occurred, or from a natural (intrinsic) or a stimulated (paced) right atrial contraction. In the latter case a left ventricular stimulation pulse is scheduled by a time interval AVD+VVD, where VVD can be positive or negative.
To deal with possibly occurring natural (intrinsic) atrial or ventricular contractions, a demand pacemaker schedules a stimulation pulse for delivery at the end of the AV-delay or the VV-delay, respectively. The delivery of the stimulation pulse is inhibited if a natural contraction of the heart chamber to be stimulated is sensed within the respective time delay.
A natural contraction of a heart chamber can be similarly detected by evaluating electrical signals sensed by the sensing channels. In the sensed electrical signal the depolarization of an atrium muscle tissue is manifested by occurrence of a P-wave. Similarly, the depolarization of ventricular muscle tissue is manifested by the occurrence of an R-wave. The detection of a P-wave or an R-wave signifies the occurrence of intrinsic atrial, As, or ventricular, Vs, events, respectively.
A dual chamber pacemaker featuring an atrial and a ventricular sensing stage and an atrial and a ventricular stimulation pulse generator can be operated in a number of stimulation modes. For example, in VVI mode, atrial sense events are ignored and no atrial stimulation pulses are generated, but only ventricular stimulation pulses are delivered in a demand mode In AAI mode, ventricular sense events are ignored and no ventricular stimulation pulses are generated, but only atrial stimulation pulses are delivered in a demand mode. In DDD mode, both atrial and ventricular stimulation pulses are delivered in a demand mode. In such a DDD mode of pacing, ventricular stimulation pulses can be generated in synchrony with sensed intrinsic atrial events and thus in synchrony with an intrinsic atrial rate, wherein a ventricular stimulation pulse is scheduled to follow an intrinsic atrial contraction after an appropriate atrioventricular delay (AV-delay; AVD), thereby maintaining the hemodynamic benefit of atrioventricular synchrony.
The AV-delay determines the chronological relation between an atrial event and a prescribed point of time of a ventricular event, the ventricular escape interval.
Since an optimal AV-delay may vary for different heart rates or stimulation rates and may even vary from patient to patient, the AV-delay usually is adjustable.
In order to promote natural ventricular events, often the ventricular escape interval is extended by a short time interval thus resulting in a prolonged ventricular escape interval called “AV hysteresis interval”.
Ventricular pacing in one or both ventricles is required for patients with AV-block and for patients who exhibit congestive heart failure (CHF patients) that are indicated for resynchronization therapy. For patients with intact sinus rhythm or with effective atrial pacing it is beneficial to stimulate the ventricle(s) synchronous with the atrial activation, i.e., after a certain delay period after the atrial event. Standard AV-synchronous dual- or three-chamber implantable devices have a programmable AVD that can be adjusted by the physician. Several studies have shown the importance of individual AVD optimization to improve the cardiac output. Especially for CHF patients an optimization of the AVD is essential. As the pumping efficacy is impaired, the optimal timing of the ventricular stimulus in relation to the atrial event contributes significantly to the cardiac performance. If the AVD is too short, the ventricle contracts before it is completely filled by the atrial blood inflow. The active filling time is reduced. Hence the stroke volume and the cardiac output are reduced. If the AVD is too long, the ventricle contracts a while after the closure of the atrioventricular valve. Hence the passive filling time of the ventricle, i.e., the diastolic filling period during the myocardial relaxation before the atrial kick, is decreased. Also, backflow of blood from the ventricle into the atrium, e.g., mitral regurgitation, is likely. Thus also in this case the cardiac output is reduced. Similar to the heart rate also the optimal AVD depends on the activation state of the circulation. If the sympathetic tone is high, e.g., during exercise, the optimal AVD is shortened compared to the resting value.
Several methods for individual AVD optimization are state of the art. The adjustment of AVD in most cases is performed during the follow-up procedure by the physician with external measurement systems, not by the implant itself. In most of the methods the patient is in rest during the adjustment procedure and only the “static” AVD is optimized. Although modern pacing devices possess a programmable dynamic AVD, i.e., an AVD that depends on the heart rate, the dynamic values are estimated in the majority of cases.
Conventionally, the AVD optimization in clinical practice has been achieved using echocardiographic techniques, particularly by measuring the pulse-wave Doppler signals of the mitral inflow. The most representative technique is the Ritter method, which estimates the optimal AVD based on the measured interval from the QRS onset to the end of A wave (active filling). Some variants of the Ritter method have also been proposed. Alternatively, the optimal AVD can be estimated by maximizing the velocity time integral (VTI) of the aortic outflow or the mitral inflow. In addition, other Doppler-based methods for AVD optimization have also been explored, based on estimation of the cardiac output, the LV pressure derivative dP/dt, and the derived myocardial performance index (MPI), which is defined as the ratio of isovolumic contraction time plus the isovolumic relaxation time to the ejection time. Another non-invasive method for assessment of cardiac output is the thoracic impedance cardiography, which has been used for optimizing the AVD, and was found to give similar results as echocardiography. Recently, finger photoplethysmography, as a simple method for non-invasive blood pressure monitoring, has been shown to be another attractive tool for optimizing AVD in cardiac resynchronization therapy (CRT) devices.
Alternatively, the AVD can be optimized based on hemodynamic indexes that are assumed to correlate to the stroke volume or cardiac output, such as the blood pressure or its temporal derivative, the ventricular volume (e.g., through chamber impedance measurement), the blood oxygen saturation, blood pH, blood temperature, etc.
The AVD can also be optimized based on some metrics derived from the surface ECG or intracardiac electrogram (IEGM) signal. For example, an algorithm is known, which calculates the optimal AVD based on the measurement of P wave duration (PWD) from the surface ECG. The concept is that the ventricular pacing should be delivered after atrial electrical activation (end of P wave) and mechanical contraction is completed. Using an empirical formula, the sensed AVD (sAVD) is simply the sum of PWD and an add-on interval of 30 ms if the PWD is greater than or equal to 100 ms, or 60 ms if the PWD is less than 100 ms. The paced AVD (pAVD) is calculated as the sum of the sAVD and the pacing latency (e.g., 50 ms). However, both sAVD and pAVD are bounded by the measured intrinsic AV interval to ensure ventricular pacing.
Another known algorithm calculates the optimal AVD based on a patient's QRS width and intrinsic AV interval. More specifically, the sensed AVD (sAVD) is expressed as a linear function of the QRS width and the sensed AV interval (sAVI), and the paced AVD (pAVD) is calculated as the weighted sum of the QRS width and the paced AV interval (pAVI). To ensure safety and efficacy, the calculated sAVD and pAVD are truncated to be within the range of 50 ms and 70% of the AV interval (sAVI or pAVI).
Most non-invasive methods described above share two common disadvantages. First, AVD optimization can only be performed after initial implantation or during device follow-up, when specially trained technicians are present to operate the external devices for the measurement. Second, patients are required to remain sedated or in stable supine position during the entire optimization procedure, which is time-consuming. Therefore, on the one hand, it adds to the already high cost of the device implantation. On the other hand, the AVD optimized in such a well-controlled environment do not guarantee to be optimal in ambulatory conditions.
The AVD optimization methods based on measurement of hemodynamic parameters usually require special sensors, and their technical reliability has not been proven.
The algorithm which calculates the optimal AVD based on the measurement of P wave duration (PWD) from the surface ECG assumes there is a linear relationship between optimal AVD and the PWD. The add-on value to the measured PWD is fixed without any consideration of the autonomic status of the heart or recovery period of the AV node, both of which have been known to affect the native AV conduction.
The algorithm that calculates the optimal AVD based on patient's QRS width and intrinsic AV interval assumes the optimal AVD is linearly related to QRS width and intrinsic AV interval. This assumption is not supported by clinical evidence. In fact, the recent SMART-AV Trial (Ellenbogen et al., “Primary Results From the SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV) Trial: A Randomized Trial Comparing Empirical, Echocardiography-Guided, and Algorithmic Atrioventricular Delay Programming in Cardiac Resynchronization Therapy,” Circulation 2010; vol. 122: 2660-2668) showed that the optimal AVD determined using this method was not superior to a fixed AVD of 120 ms.
How to achieve optimal rate-adaptation of AVD in CRT devices remains unclear. On the one hand, changes in the AV nodal conduction of intrinsic rhythm associated with exercise may alter the degree of biventricular (BiV) capture and affect the efficacy of CRT. Thus rate-adaptive AVD in CRT seems a reasonable approach for ensuring BiV capture. On the other hand, in heart failure patients, shortening of AVD at elevated heart rate may compromise the ventricular filling and result in decreased preload, and thus may have adverse effects on LV systolic function. Dynamic adjusting of AVD has also been the focus of research for decades. Although rate-adaptive AVD (i.e., shortening device AVD at increased heart rate) has been a common feature in the dual-chamber pacemakers, there is scarce literature regarding the rate-adaptation of the AVD in CRT devices.
There is still a need for an apparatus and method for optimizing pacemaker A-V delay (AVD).